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首页> 外文期刊>Ukrainian Biochemical Journal >Altered sirtuins 1 and 2 expression in the brain of rats induced by experimental diabetes and the ways of its correction
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Altered sirtuins 1 and 2 expression in the brain of rats induced by experimental diabetes and the ways of its correction

机译：实验性糖尿病诱发的大鼠大脑中sirtuins 1和2表达的改变及其纠正方法

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The molecular pathogenesis of diabetic encephalopathy (DE), one of the serious complications of diabetes mellitus, is complex. In this study, we examined whether expression levels of SIRT1 and SIRT2 were the key for the development of brain dysfunctions and whether PARP-1 inhibitors could affect the expression of these proteins for prevention the development of DE in rats with type 1 diabetes. After 10 weeks of the streptozotocin-induced diabetes mellitus (70 mg/kg), Wistar male rats were treated by i.p. injection with PARP-1 inhibitors, 1.5-isoquinolinediol (ISO) or nicotinamide (NAm) (3 or 100?mg/kg/daily i.p., respectively) for 2 weeks. The rats with blood glucose levels over 19.7 ± 2.1 mmol/l were taken into experiments. Western blots were performed to evaluate effects of PAPR-1 inhibitors on the levels of sirtuins, SIRT1 and SIRT2 expression. Diabetes induced significant reduction of SIRT1 expression and SIRT2 overexpression in brain nuclear extracts of diabetic rats compared to non-diabetic control. In brain, NAm attenuated SIRT2 overexpression in nuclear extracts of diabetic rats and slightly elevated SIRT1 expression, while ISO didn’t affect expression of both sirtuins in diabetic rats. Furthermore, it was observed that in brain of diabetic rats, the ratio of free NAD/NADH couples decreased 3.1-fold compared to non-diabetic control. The administration of ISO increased only slightly the ratio of free NAD/NADH couples in the brain of diabetic rats while NAm increased this parameter 1.7-fold compared to diabetic rats. Therefore, we concluded that alterations in the expression of SIRT1 and SIRT2 in brain cell nuclei of diabetic rats can lead to the development of brain dysfunctions. One of the neuroprotective mechanisms of NAm action can also be realized through inhibition of SIRT2 expression in brain cell nuclei that down-regulate progression of diabetes-induced alterations and can be a therapeutic option for treatment of brain dysfunctions.
机译：糖尿病性脑病（DE）是糖尿病的严重并发症之一，其分子发病机制很复杂。在这项研究中，我们检查了SIRT1和SIRT2的表达水平是否是脑功能障碍发展的关键，以及PARP-1抑制剂是否可以影响这些蛋白的表达以预防1型糖尿病大鼠DE的发展。经链脲佐菌素诱导的糖尿病（70 mg / kg）10周后，对Wistar雄性大鼠进行i.p.治疗。注射PARP-1抑制剂，1.5-异喹啉二醇（ISO）或烟酰胺（NAm）（分别为3或100？mg / kg /天，每天腹腔注射）2周。血糖水平超过19.7±2.1 mmol / l的大鼠进入实验。进行蛋白质印迹以评估PAPR-1抑制剂对沉默调节蛋白，SIRT1和SIRT2表达水平的影响。与非糖尿病对照组相比，糖尿病导致糖尿病大鼠脑核提取物中SIRT1表达和SIRT2过表达的显着降低。在脑中，NAm减弱了糖尿病大鼠核提取物中SIRT2的过表达，并略微提高了SIRT1的表达，而ISO并不影响糖尿病大鼠中两种沉默调节蛋白的表达。此外，观察到在糖尿病大鼠的脑中，与非糖尿病对照相比，游离NAD / NADH对的比率降低了3.1倍。与糖尿病大鼠相比，ISO的给药仅增加了糖尿病大鼠脑中游离NAD / NADH对的比率，而NAm使该参数增加了1.7倍。因此，我们得出结论，糖尿病大鼠脑细胞核中SIRT1和SIRT2表达的改变可导致脑功能障碍的发展。 NAm作用的神经保护机制之一也可以通过抑制SIRT2在脑细胞核中的表达来实现，该表达下调糖尿病诱导的改变的进程，并且可以作为治疗脑功能障碍的治疗选择。

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